MHIF FEATURED STUDY: OPEN AND ENROLLING: VISITAG …

MHIF FEATURED STUDY:

VISITAG SURPOINT

DESCRIPTION: Primary objective of study is to demonstrate safety and 12-month effectiveness of Tag Index-guided ablation using VISITAG SURPOINT™ Module with External Processing Unit when used with THERMOCOOL SMARTTOUCH® SF (STSF) and THERMOCOOL SMARTTOUCH® (ST) catheters for pulmonary vein isolation (PVI) in the treatment of subjects with drug refractory symptomatic paroxysmal AF.

CRITERIA LIST/ QUALIFICATIONS:Inclusion1. Symptomatic paroxysmal AF; had at least 1 AF episode electrocardiographically documented within 1 year prior to enrollment

Documentation may include ECG, TTM, Holter monitor or telemetry strip2. Failed at least 1 antiarrhythmic drug (AAD Class I or III) as evidenced by recurrent symptomatic AF, or intolerable to the AAD

CONDITION:Atrial Fibrillation (AF)

PI: Daniel Melby, MD

RESEARCH CONTACT: Jacob [email protected] | 612-863-4022

SPONSOR:Biosense Webster

OPEN AND ENROLLING: Please Refer Patients!

AF is the most common sustained arrhythmia.

It affects 0.4% to 1% of the general population, and increases in prevalence with age.

Exclusion1. Previous surgical or catheter ablation for AF2. Previous cardiac surgery (including CABG) within past 6 months (180 days)3. Valvular cardiac surgical/percutaneous procedure (i.e., ventriculotomy, atriotomy,

and valve repair or replacement and presence of a prosthetic valve)

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mailto:[email protected]

Minneapolis Heart Institute Foundation® Cardiovascular Grand Rounds Title: Current concepts in atrial fibrillation

Speaker: Daniel Melby, MD Cardiac Electrophysiologist Medical Director, Electrophysiology Lab Minneapolis Heart Institute® at Abbott Northwestern Hospital

Date: January 14, 2019 Time: 7:00 – 8:00 AM

Location: ANW Education Building, Watson Room OBJECTIVES At the completion of this activity, the participants should be able to: 1. Review pathophysiology of atrial fibrillation. 2. Understand patient selection for atrial fibrillation. 3. Explain the management of ablation patients pre and post procedure. ACCREDITATION Physician - Allina Health is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Allina Health designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Nurse - This activity has been designed to meet the Minnesota Board of Nursing continuing education requirements for 1.0 hours of credit. However, the nurse is responsible for determining whether this activity meets the requirements for acceptable continuing education. DISCLOSURE POLICY & STATEMENTS Allina Health, Learning & Development intends to provide balance, independence, objectivity and scientific rigor in all of its sponsored educational activities. All speakers and planning committee members participating in sponsored activities and their spouse/partner are required to disclose to the activity audience any real or apparent conflict(s) of interest related to the content of this conference.

The ACCME defines a commercial interest as “any entity” producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. The ACCME does not consider providers of clinical service directly to patients to be commercial interests - unless the provider of clinical service is owned, or controlled by, an ACCME-defined commercial interest.

Moderator(s)/Speaker(s) Daniel Melby, MD has disclosed the following relationship –Biosense Webster: honoraria for educational activities.

Planning Committee

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Dr. Alex Campbell, Jake Cohen, Jane Fox, Dr. Mario Gössl, Dr. Kevin Harris, Dr. Kasia Hryniewicz, Rebecca Lindberg, Amy McMeans, Dr. Michael Miedema, Dr. JoEllyn Moore, Pamela Morley, Dr. Scott Sharkey, and Jolene Bell Makowesky have disclosed that they DO NOT have any real or apparent conflicts with any commercial interest as it relates to the planning of this activity/course. Dr. David Hurrell has disclosed the following relationship -Boston Scientific: Chair, Clinical Events Committee.

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Bristol-Myers Squibb Janssen Pharmaceutical Companies of Johnson & Johnson

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MHIF CV Grand Rounds – Jan. 14, 2019

Current Concepts in Atrial FibrillationDANIEL MELBY, MD

Afib: Demographics

An estimated 2.7–6.1 million people in the United States have AFib.With the aging of the U.S. population, this number is expected toincrease.

Approximately 2% of people younger than age 65 have AFib, whileabout 9% of people aged 65 years or older have AFib.

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Journal of the American College of Cardiology. 2014;64(21):2246–80.

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Afib: Demographics by Age

Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.

U.S. population

Population withatrial fibrillation

Age, yr

<5 5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

>95

U.S. populationx 1000

Population with AFx 1000

30,000

20,000

10,000

0

500

400

300

200

100

0

Afib: Hospitalization common

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Afib: Risk factors

High blood pressure accounts for 14% to 22% of AFib cases.2

Other risk factors for AFib include2: Obesity European ancestry Diabetes Heart failure Ischemic heart disease Hyperthyroidism Chronic kidney disease Heavy alcohol use Left atrial or left ventricular chamber enlargement Obstructive Sleep Apnea

Afib: Costs and Consequences

More than 750,000 hospitalizations occur each year because of AFib.

The condition contributes to an estimated 130,000 deaths each year.

The death rate from AFib as the primary or a contributing cause of death has been rising for more than two decades.3,4

AFib costs the United States about $6 billion each year. Medical costs for people who have AFib are about $8,705 higher

per year than for people who do not have AFib.1,2

1-January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Journal of the American College of Cardiology. 2014;64(21):2246–80.2-Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–e3223-Agency for Healthcare Research and Quality. Weighted national estimates. HCUP National Inpatient Sample [online]. 2012. 4-Centers for Disease Control and Prevention. About multiple cause of death 1999–2011. CDC WONDER Online Database. 2014.

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Afib: Costs and consequences

2007 Report on 154,070 patients in France Mean Follow-up 15.2 years

In patients with atrial fibrillation HR for all cause mortality

Men 1.5 / Women 1.8

HR for cardiovascular mortality Men 2.2 / Women 3.4

ALLHAT Trial Analysis (42,000pts) Baseline AF

Mortality HR 2.8, CHF HR 3.16

Guize, et al. Bull Acad Natl Med. 2007 Apr-May; 191(4-5):791-803J Am Coll Cardiol. 2009 Nov 24;54(22):2023-31

Afib: Treatment goals

•Anticoagulation•? Other tx

Adverse Event

Prevention

•Heart rate control•Rhythm control

Symptom Control

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Afib: Adverse event prevention

Anticoagulation for thromboembolic prophylaxis CHA2DS2-Vasc Risk score based

CHF

Hypertension

Age ≥ 75 = 2

Diabetes

Stroke/TIA/Thromboembolism = 2

Vascular disease

Age 65-74

Female0

2

4

6

8

10

12

0 1 2 3 4 5 6 7

Annualized stroke rate

Chads-Vasc score

Afib: Anticoagulation, warfarin versus apixaban

NNT 100 to prevent one major bleed, 50 to prevent minor bleed

NNT 300 to prevent one CVA, 240 to prevent one death

N Engl J Med 2011; 365:981-992

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Afib: Adverse event prevention

Aside from anticoagulation No other definitive treatment to reduce other adverse events

*Except those with reduced LVEF – ablation significantly reduces mortality and CHF progression

Afib Treatment: Progression over time

Time

1940 2019

Rate control drugs

Antiarrhythmic drugs

Ablation

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Years after randomization

Cumulativemortality

(%)

0

0

1 2 3 4 5

5

10

15

20

25

30

All-cause mortality

AFFIRM Investigators. N Engl J Med 2002; 347 :1825 –33.

Rhythm control

Rate control

P=0.08

Atrial Fibrillation: Sinus Rhythm or Rate ControlAFFIRM Trial

4060pts, CHADS 1

*No difference in quality of life

AFFIRM TRIAL RESULTS

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Cabana Trial: AA drugs v. Ablation

Cabana Trial

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Cabana Trial: Caveats

27.5% of the drug therapy arm underwent ablation 9.2% of the ablation arm did not undergo ablation By Treatment received analysis, ablation arm showed:

All cause mortality reduced 40% (7.5% versus 4.4%, p=.005)

Death or CV hospitalization reduced 33% (74.9% to 41.2%, p=0.002)

47% reduction in AF

Only ~50% of patients post ablation were free of AF Only ~25% of patient on AAD were free of AF

Afib: Symptom control

Rate Control Resting HR <80 no better than

<110bpm *if no symptoms

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Afib: symptom control

Maintenance of NSR Antiarrhythmic drugs

Ablation

J Am Coll Cardiol. 2003;42:20-29.

AA drug efficacy over time

Afib: Symptom control

Ablation superior to medications

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MHI Research: Local contributions to national outcomes

2014-


2016-7

Success rates improved to 88%

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Background –Atrial fibrillation mechanism

Multiple wavelet hypothesis of Atrial fibrillation Moe proposed in 1959

AF is a sulf sustaining arrhythmia independent of focal discharges Multiple independent reentrant wavelets are necessary to maintain

fibrillation. These wavelets are always changing in position, shape, size and number with each successive excitation

Experimentally demonstrated by Allessie in 1985

Factors allowing for development of multiple wavelets Atrial size – Sufficient surface area necessary for critical number of multiple

wavelets to develop

Heterogeneous conduction velocity and tissue refractory periods allow for functional reentry

Led to the MAZE surgical procedure

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Background –Atrial fibrillation mechanism 1997 - Haissaguerre et al described

focal discharges that initiate AF 94% of AF triggers observed from

within the pulmonary veins

Shifted focus of ablation efforts to triggers

BackgroundTrigger ablation for AF

PV antral isolation In paroxysmal AF

PV isolation can achieve approximately 80% 12-month freedom from AF with optimal contact-force radiofrequency ablation or second generation cryoballoon ablation

In persistent AF

PV isolation can achieve approximately 60% 12-month freedom from AF

Less successful likely due to the presence of non-PV drivers. Insufficient success rates have led to further investigation into

methods to identify AF drivers

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Leading Circle Model of Atrial fibrillationFunctional Reentry Functional reentry

Differs from simple reentry around a fixed barrier

No excitable gap

Central core of constant activation becomes refractory and unexcitable

Small size, highest rotation frequency

Allessie MA, Bonke FI, Schopman FJ. Circ Res. 1977 Jul; 41(1):9-18.Waks JW, Josephson ME. Arrhythm Electrophysiol Rev. 2014 Aug; 3(2): 90–100

Functional reentry

Allessie, et al. Rabbit model Membrane potential

recordings D3 and D4 indicate

refractory central core activated twice as often

Low amplitude potential cannot propagate out of the center. Functionally unexcitable due to continual membrane depolarization

Allessie MA, Bonke FI, Schopman FJ. Circ Res. 1977 Jul; 41(1):9-18.Waks JW, Josephson ME. Arrhythm Electrophysiol Rev. 2014 Aug; 3(2): 90–100

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Rotors as form of functional reentry Rotors are specific form of functional reentry Described in 1992 with optical mapping Curved or spiral form Wavefront and wavetail meet at a focal point

Phase singularity

Wavefront velocity is not constant Standard functional reentry has fixed unexcitable

core Rotor core

At the phase singularity wavefront curvature is extreme and conduction velocity very slow Unable to penetrate refractory core

Phase singularity rotates around core Rotor is able to move through space as no fixed barrier

and no center of completely unexcitable tissue

Rotor initiation with PAC

Hwang M, et al PONE 2016. https://doi.org/10.1371/journal.pone.0149695

• In certain instances Rotors may anchor in place

-often to areas around the pulmonary veins and in areas of heterogeneous atrial tissue

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Complex Rotors

• Spatial and propagation instability is observed

• As the rotating wavefronts spread away from the PS and core, they interact with other in areas of anatomic or functional inhomogeneity fragment.

• They can then induce multiple disorganised‘fibrillatory’ waves which then induce the chaotic atrial activation associated with AF

AF Driver Mapping

2012 Narayan - Focal Impulse and Rotor Modulation CONFIRM trial

92 Patients 72% Persistent AF 86% Acute AF termination 82.4% single procedure freedom from AF

2017 Seitz – Spatiotemporal Electrogram Dispersion 96 patients 77.2% persistent AF 95% Acute AF termination 89% single procedure freedom from AF 55% single procedure freedom from AF/AT

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AF Driver MappingSpatiotemporal Dispersion 2017 Seitz, et al

Spatiotemporal dispersion mapping During optical mapping of isolated LA

tissue

Pseudo-multipolar electrograms demonstrated dispersion in regions of AF drivers

AF Driver MappingRipple Map

Fractionated electrogram as displayed by Ripple map

• Ripple display corresponds directly to the recorded electrogram

• No interpolation between points or other processing

• An acquired point is not assigned just a single activation time value

• Allows display of all electrical events per acquired point

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Ripple Map: Macroreentrant AT example

• There is no interpolation between points, as all data presented is “real”.

Courtesy of Drs Kanagaratnam, Luther & Linton from Imperial College Healthcare, London, UK

Potential benefits Allows complete chamber evaluation

High density, long duration, time continuous point display depolarization frequency, EGM fractionation, and voltage

Voltage/substrate display in combination with depolarization characteristics

Easily and rapidly performed using currently available catheters and software Pentaray

Confidense

Ripple map

It is possible these attributes may demonstrate AF driver sites which have proven challenging to otherwise display


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Definition: High Frequency Ripple Activation (HFRA) Atrial sites with near continuous, and high frequency atrial

depolarization as displayed by Ripple map

Hypothesis: 1) regions on Ripple with HFRA would correspond to bipolar

electrograms demonstrating CFAE and / or spatiotemporal dispersion

2) ablation of HFRA sites would terminate AF and lead to improved freedom from AF.

AF Ripple MappingAF Example, Trigger and AF driver map

-Patient with prior PVI, now with recurrent AF

-AF Trigger observed-Isoproterenol

15mcg/min-Spontaneous left atrial

-Sustained AF initiated with left atrial PACs

-Left PV reconnected-Pulmonary vein-

initiated AF

Figure: Sustained AF initiated with PACs

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AF Ripple MappingAF Example, Trigger and AF driver map

-PV initiated AF

-PVI performed, AF did not terminate

-AF driver map performed using Ripple

Figure: Sustained AF initiated with PACs

AF Driver Map with Ripple

2 AF Drivers locatedInferior posterior LAAdjacent Right Inferior Pulmonary Vein

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AF Driver Map with Ripple

AF terminates with HFRA sites AF Trigger eliminated with PV isolation

Isoproterenol 15mcg no spontaneous PACs or AF

AF Drivers modified Noninducible atrial pacing 200ms

AF Driver Map with Ripple - Persistent AFDriver – Left PV antrum AF present for prior 4 months Trigger not revealed while in

sustained AF AF Ripple map performed for AF

drivers

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Ripple Map Study

A total of 161 consecutive patients underwent a first-time ablation for persistent AF

Ripple map guided (n=56)

standard stepwise (n=105) approach

Ripple map approach PV antral isolation Ablation of HFRA locations Up to 3 Remaps performed if needed Ablation proceeded until AF termination or loss of all HFRA sites within LA and RA

Stepwise approach Haïssaguerre technique PV antral isolation Posterior LA LA roof CFAE Mitral isthmus

Ripple Map Study : Baseline characteristics

Ripple map

(n=56)

Standard stepwise

(n=105)

P Value

Age (mean in yr ±SD) 65.1 ± 10.3 64.8 ± 9.2 0.90

Male – no. (%) 67.8 85.7 0.008

Structural Heart Disease* (%) 14.3 17.1 0.64

Diabetes – no. (%) 16.1 21.0 0.45

Hypertension – no. (%) 46.4 62.3 0.045

Baseline LA dimension (cm ±SD) 4.3 ± 0.5 4.5 ± 0.6 0.068

Baseline LVEF (%±SD) 53.4 ± 11.3 55.2 ± 10.7 0.32

Prior BB or CCB use (%) 91.1 90.5 0.90

Failed AAD (class Ic or III) (%) 89.3 78.1 0.078

Duration since 1st AF diagnosis (months) 30.9 ± 41.6 41.2 ± 49.4 0.19

Duration continuous AF prior to RFA (months) 5.00 ± 5.7 7.3 ± 10.8 0.14

Cha2ds2-Vasc score 2.3 ± 1.5 2.4 ± 1.6 0.74Table 1: Characteristics of the patients who underwent Ripple map guided AF ablation. **SHD=Congestive heart failure, Constrictive pericarditis, Amyloid cardiomyopathy, Cardiac surgery

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95.8

91.4

80

82

84

86

88

90

92

94

96

98

100

Paroxysmal Persistent

Afib

Term

inat

ion

(%)

Acute AF Termination

N=75 N=56

Ripple Map StudyResults – Acute Termination All AF Types

Ripple Map StudyResults - HFRA characteristics

Persistent AF 4.2 Mean HFRA Regions

Paroxysmal AF 1.9 Mean HFRA Regions

0

20

40

60

80

100

PV Antrum LA Roof LA Septum Inferior LA Posterior LA

Most Common HFRA Regions in Persistent AF

%

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Ripple Map StudyResults – 18 Month Single Procedure

After a single procedure, at 18 months significantly more patients in the Ripple map guided strategy were free of AF, compared to the standard stepwise strategy (98.2% versus 81.9, p=0.009).

This difference remained after adjusting for gender and presence of HTN.

Best Randomized Study for Persistent AF –Single Procedure Freedom from AF

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Ripple Map StudyResults – 18 Month Single Procedure

There was no difference in freedom from AT (53.6% versus 52.4%, p=0.89) or freedom from any atrial arrhythmia (51.8 versus 40.0, p=0.12).

Ripple Map StudyMultiple procedure outcome

After an average of 1.4 ablations procedures Freedom from any AF was significantly higher in the Ripple group

compared to the standard group (100% versus 88.6%, p=0.015)

There was no difference in freedom from AT (86.9% Ripple versus 76.2% standard, p=0.11) or any atrial arrhythmia (83.4% versus 70.5, p=0.09).

19 patients with AF or AT Recurrence in Ripple map group underwent second ablation After 2 ablations, 17 of 19 (89.5%) were free of AF/AT

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MHI Research: Improving outcomes national ablation outcomes -

2000-14 65%

success

2014 81%

success

2016-17 88%

success

2018 93-95+%

success

MHI Research: 2019 and beyond

Improved accuracy of afib ablation targets using Ripple map technique developed at MHI Manuscript of 18 month follow up nearly complete for submission

Research Version of Biosense Carto Mapping system under development with engineers in Israel

Multicenter national trial proposed for 2019

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Biosense Visitag SurePoint Study Enrolling Now

National Multicenter Study

Paroxysmal Afib, Failed AAD

New Method for accurately estimating lesion size First Ever Available

May demonstrate consistently high success rates due to improved lesion consistency


Biosense QDOT Study Expected March 2019 Initial enrollment National Multicenter Study New Catheter for Afib ablation

Allows for surrogate lesion temperature assessment QMODE: Automatic adjustment of power and tip

cooling flow to keep temperature under char and steam pop zone

First Ever Available QMODE + : Allows for safe high power, short duration

ablation (90Watts, 4 Seconds versus current 30-35watts, 25-35 seconds)

In Europe, PAfib left atrial procedure times were reduced to from 120 to 45 minutes

Paroxysmal Afib, Failed AAD

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Conclusions

Afib is common, and associated with increased risk of stroke, mortality, and CHF

Anticoagulation reduces stroke rate No treatment definitively reduces mortality For symptom control, ablation more effective than AA drugs With current research avenues, improved treatment options are

emerging

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